The overall objective of the work put forth in this proposal is to provide a framework, both theoretical and experimental, for the identification and quantitative analysis of the molecular mechanisms of ion transport in heart and other excitable membranes. This overall objective is approached through a comparative study of the permeability characteristics of lipid bilayer membranes in which ionic transport occurs by one of the three main permeation mechanisms: direct transfer, carrier-mediated transfer or transfer through conductive channels. In order to reveal typical characteristics as well as the full range of complexities encountered for different permeation mechanisms, the comparative study concentrates on a systematic and broad-range characterization of the relationship between membrane lipid composition and ionic transport induced by a spectrum of lipid soluble ions, ion-carriers and channel-formers. Kinetic parameters, deduced from steady-state and transient conductance measurements, are used to characterize membrane permeability. For lipid soluble ions, these parameters are the rates of translocation and surface adsorption. For carriers, the corresponding parameters are rates of translocation of the carrier and of the ion-carrier complex; as well as rates of formation and dissociation of the complex at the membrane surface. For ionic channels, membrane permeability is characterized by single-channel conductance together with kinetic parameters of channel forming and breakdown. An in-depth study is proposed for those lipid soluble ions, carriers and channel-formers which show simple, easily interpreted behavior since such "ionophores" may be used routinely as "probes" of the electrochemical properties of lipid bilayer and cell membranes.